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Multiomics analysis identifies BIRC3 as a novel glucocorticoid response-associated gene.
Kan, Mengyuan; Diwadkar, Avantika R; Shuai, Haoyue; Joo, Jaehyun; Wang, Alberta L; Ong, Mei-Sing; Sordillo, Joanne E; Iribarren, Carlos; Lu, Meng X; Hernandez-Pacheco, Natalia; Perez-Garcia, Javier; Gorenjak, Mario; Potocnik, Uros; Burchard, Esteban G; Pino-Yanes, Maria; Wu, Ann Chen; Himes, Blanca E.
Afiliação
  • Kan M; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pa.
  • Diwadkar AR; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pa.
  • Shuai H; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pa.
  • Joo J; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pa.
  • Wang AL; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass; Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass.
  • Ong MS; Precision Medicine Translational Research Center, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Mass.
  • Sordillo JE; Precision Medicine Translational Research Center, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Mass.
  • Iribarren C; Kaiser Permanente Division of Research, Kaiser Permanente, Oakland, Calif.
  • Lu MX; Kaiser Permanente Division of Research, Kaiser Permanente, Oakland, Calif.
  • Hernandez-Pacheco N; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
  • Perez-Garcia J; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
  • Gorenjak M; Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
  • Potocnik U; Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia; Laboratory for Biochemistry, Molecular Biology, and Genomics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia.
  • Burchard EG; Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
  • Pino-Yanes M; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, San Cristóbal de La Laguna, Spain; Instituto de Tecnologías Biomédicas, Universidad de La Lagun
  • Wu AC; Precision Medicine Translational Research Center, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Mass.
  • Himes BE; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pa. Electronic address: bhimes@pennmedicine.upenn.edu.
J Allergy Clin Immunol ; 149(6): 1981-1991, 2022 06.
Article em En | MEDLINE | ID: mdl-34971648
BACKGROUND: Inhaled corticosteroid (ICS) response among patients with asthma is influenced by genetics, but biologically actionable insights based on associations have not been found. Various glucocorticoid response omics data sets are available to interrogate their biological effects. OBJECTIVE: We sought to identify functionally relevant ICS-response genetic associations by integrating complementary multiomics data sets. METHODS: Variants with P values less than 10-4 from a previous ICS-response genome-wide association study were reranked on the basis of integrative scores determined from (1) glucocorticoid receptor- and (2) RNA polymerase II-binding regions inferred from ChIP-Seq data for 3 airway cell types, (3) glucocorticoid response element motifs, (4) differentially expressed genes in response to glucocorticoid exposure according to 20 transcriptomic data sets, and (5) expression quantitative trait loci from GTEx. Candidate variants were tested for association with ICS response and asthma in 6 independent studies. RESULTS: Four variants had significant (q value < 0.05) multiomics integrative scores. These variants were in a locus consisting of 52 variants in high linkage disequilibrium (r2 ≥ 0.8) near glucocorticoid receptor-binding sites by the gene BIRC3. Variants were also BIRC3 expression quantitative trait loci in lung, and 2 were within/near putative glucocorticoid response element motifs. BIRC3 had increased RNA polymerase II occupancy and gene expression, with glucocorticoid exposure in 2 ChIP-Seq and 13 transcriptomic data sets. Some BIRC3 variants in the 52-variant locus were associated (P < .05) with ICS response in 3 independent studies and others with asthma in 1 study. CONCLUSIONS: BIRC3 should be prioritized for further functional studies of ICS response.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Glucocorticoides Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Allergy Clin Immunol Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Glucocorticoides Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Allergy Clin Immunol Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos